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Luminescent silicon quantum dots (Si QDs) have great potential for use in biological imaging and diagnostic applications. To exploit this potential, they must remain luminescent and stably dispersed in water and biological fluids over a wide range of pH and salt concentration. There have been many challenges in creating such stable water-dispersible Si QDs, including instability of photoluminescence due their fast oxidation in aqueous environments and the difficulty of attaching hydrophilic molecules to Si QD surfaces. In this paper, we report the preparation of highly stable aqueous suspensions of Si QDs using phospholipid micelles, in which the optical properties of Si nanocrystals are retained. These luminescent micelle-encapsulated Si QDs were used as luminescent labels for pancreatic cancer cells. This paves the way for silicon quantum dots to be a valuable optical probe in biomedical diagnostics.

A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drug-carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter approximately 30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated.

Successful translation of the use of nanoparticles from laboratories to clinics requires exhaustive and elaborate studies involving the biodistribution, clearance and biocompatibility of nanoparticles for in vivo biomedical applications. We report here the use of multimodal organically modified silica (ORMOSIL) nanoparticles for in vivo bioimaging, biodistribution, clearance and toxicity studies. We have synthesized ORMOSIL nanoparticles with diameters of 20-25 nm, conjugated with near infra-red (NIR) fluorophores and radiolabelled them with 124 I, for optical and PET imaging in vivo. The biodistribution of the non targeted nanoparticles was studied in non-tumored nude mice by optical fluorescence imaging, as well by measuring the radioactivity from harvested organs. Biodistribution studies showed a greater accumulation of nanoparticles in liver, spleen and stomach than in kidney, heart and lungs. The clearance studies carried out over a period of 15 days indicated hepatobiliary excretion of the nanoparticles. Selected tissues were analyzed for any potential toxicity by histological analysis, which confirmed the absence of any adverse effect or any other abnormalities in the tissues. The results demonstrate that these multimodal nanoparticles have potentially ideal attributes for use as biocompatible probes for in vivo imaging. KeywordsORMOSIL Nanoparticles; optical and PET Imaging; NIR fluorophore; 124 I radiolabeling; Biodistribution; clearance and toxicity Nanomaterials promise to address the current limitations of sensitivity and specificity of medical diagnostics, as well as significantly improve the outcome of existing and emerging therapeutics, via the introduction of new generation of multimodal nanoprobes. [1][2][3][4][5][6] In this regard, it is critical to design nanoprobes with desired composition, size and surface functionalities, and rigorously test them in vitro and in vivo for their safety and efficiency. Also biocompatibility and biodegradation of the nanoprobe materials play an important role in the use of the nanoprobes in the field of diagnostic and therapeutic applications.The rise in nanoprobes development has bolstered the prospects of in vivo optical imaging through the development of a variety of NIR-luminescent nanoformulations, which include quantum dots, 7 upconverting nanophosphors, 8 Herein, we report the synthesis of ultrafine ORMOSIL nanoparticles (diameter ∼20 nm), conjugated with a near-infra-red (NIR) fluorophore, as optical probes. The resulting NIRnanoparticles will facilitate optical bioimaging in the NIR window, with maximum tissue penetration of light and minimum background signal. 23, 24 Furthermore, we have also conjugated the well-known positron emission tomographic (PET) imaging probe Iodine-124 with the nanoparticle, which will allow bioimaging independent of tissue-depth, as well as more accurate quantification of accumulation of nanoparticles in various major organs in vivo. These multimodal nanoprobes have been injected systemically in mice, and their in v...

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Nanoparticle technology plays a key role in providing opportunities and possibilities for the development of new generation of sensing tools. The targeted sensing of selective biomolecules using functionalized gold nanoparticles (Au NPs) has become a major research thrust in the last decade. Au NP-based sensors are expected to change the very foundations of sensing and detecting biomolecules. In this review, we will discuss the use of surface functionalized Au NPs for smart sensor fabrication leading to detection of specific biomolecules and heavy metal ions.

Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivo targeted fluorescence imaging, traceable delivery, and therapy. The use of group II-VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II-VI QDs contain toxic heavy metals that limit their in vivo applications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivo imaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivo models, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.

Quantum dots have been used in biomedical research for imaging, diagnostics and sensing purposes. However, concerns over the cytotoxicity of their heavy metal constituents and conflicting results from in vitro and small animal toxicity studies have limited their translation towards clinical applications. Here, we show in a pilot study that rhesus macaques injected with phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood and biochemical markers remained within normal ranges following treatment, and histology of major organs after 90 days showed no abnormalities. Our results show that acute toxicity of these quantum dots in vivo can be minimal. However, chemical analysis revealed that most of the initial dose of cadmium remained in the liver, spleen and kidneys after 90 days. This means that the breakdown and clearance of quantum dots is quite slow, suggesting that longer-term studies will be required to determine the ultimate fate of these heavy metals and the impact of their persistence in primates.